Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996     

Laparoscopic incisional hernia repair after liver transplantation.

Incisional hernias occur in up to 17% of patients after liver transplantation. Laparoscopic ventral hernia repair is associated with fewer wound complications and a decreased incidence of recurrence when compared to open hernia repair in nontransplant patients. This is a retrospective review of 13 patients who underwent laparoscopic incisional hernia repair (LAP group) after liver transplantation compared to 14 patients who had open repairs (OP group; all but one with mesh). Primary immunosuppression in both groups at the time of transplantation was tacrolimus, but more patients in the LAP group were on sirolimus at the time of hernia, while more patients in the OP group were on prednisone at the time of hernia repair. All operations were completed with a laparoscopic approach; there were no conversions to open. Length of stay differed significantly between the 2 groups, with a mean of 5.4 days for the LAP group compared to 2.7 days in the OP group (0.0059). Complications occurred in 2 (15%) of the patients in the LAP group and 5 (36%) in the OP group. One patient in the LAP group required mesh removal to exclude causes of recurrent ascites, and 1 in the OP group for mesh infection. One (7.6%) of the patients in the LAP group developed a recurrence, compared to 29% (4) of the OP group (P =0.3259). In conclusion, laparoscopic incisional hernia repair is safe in patients after liver transplantation, with a low risk of infection or recurrence.     

Initial evaluation of123|-5-|-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects

The mapping of 5-HT₂ receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150 or¹²³I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT_2A receptors. This study reports on preliminary¹²³I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT_2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT_2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that¹²³I-5-I-R91150 may be used for the imaging of 5-HT_2A receptors in the living human brain with SPET.     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

Weight loss in a murine cachexia model is not associated with the cytokines tumour necrosis factor-alpha or interleukin-6.

Daily administration of an escalating dose of tumour necrosis factor-alpha (TNF-alpha) to female NMRI mice caused a progressive loss of body weight representing 12% of the original weight over a 6-day period. Weight loss was associated with a decreased food intake and pair-fed controls exhibited a weight loss of similar magnitude to that caused by TNF-alpha. However, weight loss in animals bearing a murine adenocarcinoma (MAC16) occurred without a change in energy intake and thus differed from that produced by TNF-alpha. Anti-TNF-alpha monoclonal antibodies at levels capable of protecting mice against lethal endotoxaemia were ineffective in reversing weight loss in animals bearing the MAC16 tumour and had no effect on the increase in tumour volume. Circulating levels of interleukin-6 were not elevated in animals bearing the MAC16 tumour and with a weight loss between 1.8 and 5.4 g. These results suggest that these cytokines are not involved in the cachexia produced by this murine tumour.     

New developments in sustained-release antihypertensive therapy: formulation and pharmacokinetic considerations.

In order to achieve a consistently absorbed form of nifedipine over 24 hours, a novel formulation approach, INDAS, was used to develop a once-daily, sustained-release (SR) form of nifedipine that could provide effective control of blood pressure at a low total daily dose. The pharmacokinetic characteristics of this new formulation of nifedipine-SR were compared with those of divided doses of conventional nifedipine. The SR formulation was shown to achieve a lower peak plasma nifedipine level but with a prolonged plasma profile characterized by an extended time to peak plasma levels (Tmax), a higher trough plasma level, a longer apparent half-life, and a markedly lower peak-to-trough fluctuation in plasma nifedipine concentrations. In a separate study, the gastrointestinal transit parameters and physical characteristics of the SR tablet were evaluated. This study established that the large intestine is the major site of residence and absorption for this dosage form. The physical erosion and disintegration characteristics of the SR formulation are such that a well-maintained absorption of nifedipine is consistently achieved over the 24 hour dosing interval.